Device and method for separation

ABSTRACT

The present invention provides a device and a method for separating particles from fluids using ultrasound, laminar flow, and stationary wave effects comprisinga micro-technology channel system with an integrated branching point or branching fork, and a single ultrasound source. One of the characteristics of the invention is that the single ultrasound source, which generates the standing waves, excites the complete structure including the channel system. No special reflectors or the like are needed. Extremely thin dividers can separate the flow, thereby enhancing the effectiveness of the device. The device could be manufactured in silicon and the ultrasound energy could preferably be delivered by a piezoelectric element.

FIELD OF THE INVENTION

[0001] The present invention relates to a device and a method forseparating a fluid containing suspended particles into fractions ofhigher and lower concentration of said suspended particles usingultrasonic standing waves and micro-technology.

STATE OF THE ART

[0002] It is known that when particles in a fluid are subjected to anacoustic standing wave field, the particles are displaced to locationsat, or in relation to the standing wave nodes. A number of attempts touse ultrasound standing wave field for the manipulation or separationare known.

[0003] In WO 00/04978 is described a device for performing themanipulation of particles suspended in a fluid. It comprises a duct forthe flow of a fluid in which particles are suspended, and an acoustictransducer and a reflector for establishing an acoustic standing wavefield across the width of said duct, the spacing between the transducerand reflector being 300 μm or less.

[0004] In an abstract to the 4^(th) annual European conference on micro& nanoscale technologies for the biosciences (NanoTech 2000), Hawkes andCoakley describes a “force field particle filter, combining laminar flowand ultrasound standing waves” with an acoustic path length at rightangles to the flow of 0.25 mm.

[0005] In WO 98/50133 is described a device for performing themanipulation of particles suspended in a fluid. It comprises a duct forthe flow of a fluid, in which particles are suspended, said duct havingmeans for establishing an acoustic standing wave field so that theparticles are displaced to form parallel bands. The duct includes anexpansion in width.

[0006] In IBM, technical disclosure bulletin vol. 25, No. 1, June 1982,page 192/193 is disclosed an ultrasonic continuous flow plasmapheresisseparator comprising two orthogonally mounted ultrasound transducerswith one reflector each and a volume between where a dilute suspensionis subjected to an acoustic standing wave field.

[0007] In JP 06241977 A is described a fine particle measuringinstrument that uses a standing ultrasonic wave with a node at thecentre of a flow cell to centre and concentrate fine particles.

[0008] In EP 0 773 055 A2 and A3 is described a method and an apparatusfor handling particles by an acoustic radiation force. The apparatuscomprises a chamber for accommodating a fluid containing the particlesto be concentrated, filtered or arranged, and a plurality of ultrasoundsources disposed to make direct or indirect contact with the fluid. Theapparatus also comprises a control device for controlling saidultrasound sources to generate an ultrasound beam obtained bysuperimposing ultrasound beams from said ultrasound sources on oneanother, said beams each having a specific intensity, a specificfrequency and a specific phase.

[0009] In WO 93/19367 A2 and A3 is described a method and an apparatusfor particle aggregation, said apparatus comprising a tube forcontaining of a sample of a liquid, and an ultrasonic transducerarranged to generate a standing wave ultrasound field transverse to thetube. The standing wave exhibiting a progressive change in pressureamplitude transverse to the tube, so that, in use of the apparatus,particles in suspension are displaced transversely of the tube to one ormore predetermined regions. After termination of exposure to thestanding wave particles are allowed to settle and can then be inspected.Appreciated use of the apparatus includes carrying outimmuno-agglutination assays. The document is based on U.S. Pat. No.5,665,605 and U.S. Pat. No. 5,912,182.

[0010] In JP 07 047259 A is described an apparatus for transporting fineparticles in fluid with ultrasonic waves. The apparatus comprises amultitude of ultrasonic wave generating elements two-dimensionallyarranged on two flat plates. Between the plates a solution can bedeposited.

SUMMARY OF THE INVENTION

[0011] The present invention provides a device and a method forseparating particles from fluids using ultrasound, laminar flow, andstationary wave effects comprising micro-technology channels formed inthe surface portion of a plate, having integrated branching points orbranching forks, and an ultrasound source arranged in close contact toan opposing surface of said plate.

[0012] Standing waves are generated in the channels so that particlessuspended in the fluid are brought into certain lamina of said fluid,and that one or more lamina are formed devoid of particles, or areformed carrying particles of different properties than the firstmentioned ones. Said laminae are thus arranged perpendicular to saidplate, this is important because the branching of a channel must takeplace within the plate, so that a connection with another channel cantake place also within the same plate. The advantages of this will beobvious below.

[0013] One of the characteristics of the invention is that theultrasound source is arranged in perpendicular contact with the plate,conveying ultrasound energy in a direction that is perpendicular theplate. The inventors have tested and proved that in the presentinvention, as a result of the dimensions of the channels and theproperties of the plate and the ultrasound transmitter, a standing waveis generated that reaches from one side wall of a channel to theopposing side wall of the same channel. It would normally be expectedthat such an arrangement would generate (only) a standing wave reachingfrom a bottom wall to a top wall of said channel, continuing in adirection of the original energy flow.

[0014] The inventors have also realised the great importance of thisidea. Because, according to the invention, the ultrasound source now donot have to be a part of the plane or layer where the channels reside,and space becomes available for packing more channels into a limitedspace, greatly enhancing the possibilities of manufacturing devices witha multitude of parallel channels providing high capacity particleseparation. A high degree of particle separation could also easily beprovided by a serial arrangement of separation units, as will be furtherexplained below. The capability of high yield parallel and serialprocessing of a fluid using ultrasound is thus a central part andconsequence of the inventive concept.

[0015] The above is possible because the channels and branching pointsare formed in a plate comprising one piece of material or in a fewpieces of material closely bonded together. No special reflectors or thelike are used. It may also be possible to use more than one ultrasoundsource. Thin dividers are arranged to separate the laminar flows afterthe branching points, thereby enhancing the effectiveness of the device.The device is preferably manufactured using silicon technologybenefiting from the possibility of small precise dimensions, and theultrasound energy could preferably be delivered by a piezoelectricelement, which in turn could be driven from a control unit capable ofdelivering electrical energy of certain shape, frequency and power.

[0016] The invention is defined in the accompanying claim 1, whilepreferred embodiments are set forth in the dependent claims.

BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The invention will be described below with reference to theaccompanying drawings, in which:

[0018]FIG. 1 shows a top view of a cross channel system arrangement;

[0019]FIG. 2 shows a perspective view of the object in FIG. 1;

[0020]FIG. 3 shows a bottom view of the object in FIG. 1;

[0021]FIG. 4 shows a side view of the object in FIG. 1;

[0022]FIG. 5 shows a top view of a repeated arrangement;

[0023]FIG. 6 shows a detail top view of a parallel arrangement branchingpoint;

[0024]FIG. 7 shows standing waves in the space between two walls;

[0025]FIG. 8 shows a cross section view of the device;

[0026]FIG. 9 shows schematically separation using one-node standingwave;

[0027]FIG. 10 shows schematically separation using two-node standingwave;

[0028]FIG. 11 shows schematically a one-node three-step serial wash;

[0029]FIG. 12 shows schematically a one-node three-step concentrator;

[0030]FIG. 13 shows schematically a one-node four-step integrated washand concentrator;

[0031]FIG. 14 shows a top view of an embodiment with labelled branchingangles;

[0032]FIG. 15 shows a parallel arrangement of eight channel units;

[0033]FIG. 16 shows the parallel arrangement of FIG. 15 in perspective;

[0034]FIG. 17 shows schematically a serial arrangement of two channelunits;

[0035]FIG. 18 illustrates a separation of two different kinds ofparticles with different density;

[0036]FIG. 19 illustrates a channel unit with the inlets and theoutlets;

[0037]FIG. 20 illustrates the channel unit of FIG. 19 includingparticles;

[0038]FIG. 21 shows schematically a radial arrangement of the channelunits;

[0039]FIG. 22 shows the embodiment of FIG. 21 in perspective.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0040] Referring to FIGS. 1, 2, and 8, one embodiment of the inventioncomprises a plate 51,851, with an integrated channel system, with a basestem 110 and a left arm 120, a right arm 130 and a central arm 140. Thewalls of the base stem 810, 820 are essentially perpendicular to theplate 51 and parallel or near parallel to each other, and to the flow,which is a prerequisite for the establishment of standing waves acrossthe channel along its entire depth and length, see below.

[0041] At the back of the plate 51, means for delivering ultrasoundenergy to the plate is arranged in the form of a piezoelectric element150, 853. The device will function as follows:

[0042] A fluid with suspended particles entering the base stem 110 atthe inlet 160 will flow towards the branching point 175 because of anarranged pressure gradient, which gradient could be created by e.g. asuction pump, a pressure pump, a syringe or by gravity. By controllingthe frequency of the ultrasound and use of certain frequencies suitableto the dimensions of the base stem 110, particularly the width 185 ofsaid stem 110, a stationary wave pattern is formed in the fluid insidesaid stem 110. Especially there will form a stationary wave patternorthogonal to the direction of the flow between a left 810 and a right820 side wall of the base stem 110. Pressure nodes will form in greaternumbers in the middle part of the channel than at the walls, wherepressure antinodes will form. During said flow, particles in the fluidwill tend to accumulate in nodes of said stationary wave-pattern, or incertain layers in relation to the nodes depending on the particles'density/densities/acoustic impedance relative to the surrounding fluid.Particles with a higher density than said surrounding fluid will tend toaccumulate in the nodes, whereas particles with a density lower than thesurrounding fluid will tend to accumulate in the antinodes. The layersof fluid discussed in the following are the layers parallel to thesidewalls 810, 820 of the base stem 110.

[0043] Depending on the density/acoustic impedance, size and weight ofthe particles, certain patterns of accumulations of particles will beformed. This is an advantage when separating out particles of a certainweight and/or size from a medium containing a spectrum of particles ofdifferent density/acoustic impedance. Generally, particles having adensity higher than the density of the surrounding fluid, accumulates inthe nodes, and particles having a density lower than the fluid withoutparticles, accumulate in the antinodes. By providing a branching forkwith two side branches or arms and one central branch or arm 140 asshown in FIGS. 1, 6 or 8, it is possible to separate out said particles.The post-branch point arms or channels are preferably arranged withspacing adapted to the wavelength, i.e., a centre to centre distance ofapproximately ⅜ of a wavelength.

[0044] Depending on the resonance conditions, confer FIG. 7, differentresults of the above will be obtained. For a single node condition, theresult of the above is that the layers of fluid near the walls of thebase stem 110 will contain a decreasing concentration of high densityparticles as the fluid flows along said stem 110 towards the branchingpoint 175. At said branching point 175, fluid that mainly originatesfrom the central parts of the fluid-stream in the stem 110 will, due tolaminar flow, continue its movement straight ahead and enter the centralarm 140. Fluid originating from the fluid-stream appearing near thewalls of the stem 110, will deflect into the left arm 120 (from the leftwall) and into the right arm (from the right wall). Fractions of fluidcontaining a low concentration of high-density particles can then becollected at the left outlet 170 and the right outlet 180. The fractionof fluid containing a high concentration of high-density particles canbe collected at the top outlet 190. In FIG. 9 is shown how a number ofhigh density particles (higher density than surrounding fluid)accumulates in a central division or channel with a central outlet 91,whereas fluid with a low or zero concentration of said particles flowsout at the lateral divisions and outlets 92. As a comparison, FIG. 10shows one way of using a two-node standing wave pattern to move theparticles so that they can be collected at two lateral divisionsprovided with outlets 102. Fluid with a low or zero concentration ofsaid particles flows out at the central division and outlet 101. Asimilar effect could also be achieved using five divisions or channels,where the most lateral channels and the central channel collect fluidwith low or zero concentration of high density particles, and the othertwo channels collect fluid with high concentration of said particles,i.e. n=3 below.

[0045] By controlling the frequency of the ultrasound that creates thestanding wave field it is possible to generate a standing wave betweenthe side walls of the base stem 110 with a standing wave length of 0.5,1.5, 2.5 etc. wavelengths, i.e., n times 0.5 wavelengths, n=1, 3, 5, 7 .. . cf. FIG. 7. A device according to the invention making use of theinvention's ability to separate particles into the nodes and antinodescould therefore have a number of channels after the branching pointcorresponding to the number of nodes plus the number of antinodes in thestanding wave field. For example, frequencies having 0.5, 1,5 and 2.5wavelengths across the base stem 110 could have 3, 5 and 7 channelscorrespondingly.

[0046] Preferred embodiments of the invention therefore include meansfor controlling the frequency of the ultrasound generating means. InFIG. 8 is shown how a control unit 863 (shown in a different scale) canbe connected to the piezoelectric element 853. Said control unit 863 iscapable of delivering electrical energy to said element 853. Saidelectrical energy is controllable with regard to waveform, frequency andpower, where said waveform is controllable to be one of, but not limitedto sinus wave, triangular wave or square wave.

[0047] Other embodiments of the invention include bifurcation and“trifurcation” of different shape, integrated on the same piece ofmaterial, and with the overall purpose to divide the laminar flow offluid.

[0048] In FIG. 6 is shown a detail of another embodiment where thebranching point comprises the branching of the base stem 110 directlyinto three parallel arms 610, 620, 630 divided by thin dividing walls.By the use of the techniques described below it is possible to arrangethese thin walls with a thickness of down to 1 μm and even lower. Thinwalls will give better performance due to better preservation of thelaminar flow profile across the full channel width.

[0049]FIG. 14 shows an embodiment with a left branching angle α1 betweena left arm 143 and a central arm 144 and a right branching angle α2between said central arm 144 and a right arm 145. By varying the anglesα1 and α2 it is possible to optimise certain factors such as e.g. thedegree of particle concentration. However, certain angles can bedifficult to manufacture with certain manufacturing processes. Anglesbetween 0 and 90 degrees show good ability to separate flow.

[0050] In FIG. 3, which shows the device from beneath, are shown theconnections 31-34 to the inlet 160 and to the outlets 170, 180, 190 fromFIG. 1. The piezoelectric element is not shown for the sake of clarity.

[0051] In FIG. 4 the device is shown from the side. The devicepreferably comprises two layers, one layer 51 including the channelsystem, made e.g. of silicon, and one sealing layer 52 made of e.g.glass which makes it possible to visually inspect the process. Thesealing glass layer could preferably be bonded with known techniques tothe base layer 51. The piezoelectric element 53 is arranged in acousticcontact with the base layer 51.

[0052] In FIGS. 5, 11, 12, and 13 arrangements are shown where certaineffects can be achieved through a consecutive or serial use of repeatedstructures. For example, high and low density particles can be separatedusing the arrangement in FIG. 5. (high and low density indicate merelythe density relatively to the surrounding fluid). Here, fluid is enteredat a main inlet 60. If a one-node resonance condition is present, fluidwith high concentration of high-density particles will accumulate atoutlet 61. Fluid with low concentration of high-density particlestogether with high concentration of low-density particles willaccumulate at outlet 62, and fluid with intermediate concentration ofhigh-density particles will accumulate at outlet 63. A piezoelectricelement 65 is arranged in acoustic contact with the common supportingstructure, giving rise to standing wave fields in channels withappropriate dimensions, i.e. the channel parts 66 and 68. To compensatefor fluid loss, inlets 69 are provided for adding pure fluid withoutparticles. The inlets could also be used for cleaning of the system.

[0053] Parallel arrangements of single or serial structures according toFIGS. 5, 11, 12, and 13 can easily be achieved. Channel systemsaccording to embodiments of the invention could e.g. repeatedly andinter-connectedly be arranged, filling the area of the plate, whichplate can comprise e.g., a silicon wafer or other area sheets or discsof other materials such as e.g. plastics. Parallel arrangements will addcapacity, i.e. more fluid volume can be processed per time interval.

[0054]FIG. 11 shows schematically a one-node three-step serial washer.Contaminated fluid with particles of interest to save (e.g. red bloodcells) enters at inlet 111. Contaminated fluid with low or zeroconcentration of particles leaves at outlets 112. Particles continue toflow, passing inlet 113 which adds clean fluid to the particles and somestill remaining contaminants will become more diluted. Separation willbe repeated in a second step where contaminated fluid with low or zeroconcentration of particles leaves at outlets 114. Particles continue toflow, passing inlet 115, which adds clean fluid to the particles and ifstill some remaining contaminants, these will become even more diluted.Separation will then be repeated in a third step, and particlessuspended in now very clean fluid will leave at outlet 117.

[0055]FIG. 12 shows schematically a one-node three-step serialconcentrator. Contaminated fluid with particles of interest to save(e.g. red blood cells) enters at inlet 121. Particles are concentratedat outlets 122, 124 and 128. Contaminated fluid is removed at outlets126.

[0056]FIG. 13 shows schematically a one-node four-step integrated washerand concentrator. Contaminated fluid with particles of interest to save(e.g. red blood cells) enters at inlet 131. Contaminated fluid with lowor zero concentration of said particles leaves at outlets 132. Cleanfluid is added at inlet 134. In a second step, (less) contaminated fluidwith low or zero concentration of particles leaves at outlets 133. Cleanfluid is added at inlet 136. In steps 3 and 4 particles are concentratedand removed through outlets 137 and 138. Excess fluid is removed throughoutlets 139.

[0057] Returning now to FIG. 1, the channel system, including the basestem 110 and the branching point, is preferably integrated on a singlepiece of homogenous material 51 in FIG. 4. This entails the advantage ofease to repeat a number of channel systems thereby easily increasing thecapacity of a separation apparatus making use of the invention.

[0058] Preferred embodiments include embodiments with channel systemsintegrated with a single substrate or deposited on a substrate by acontinuous series of compatible processes.

[0059] The device according to the present invention can be manufacturedfor example in silicon. The requirement to make the walls of the basestem (810, 820) essentially perpendicular to the plate and parallel ornear parallel to each other is easily fulfilled by using silicon of a<110> crystal structure and well known etching techniques. The desiredchannel wall structure described may also be realised by deep reactiveion etching, DRIE.

[0060] It is also possible to form the layers in plastic materials, forinstance by using a silicon matrix. Many plastics have good chemicalproperties. The silicon layer structure can be produced by means ofwell-known technologies. Channels and cavities can be produced by meansof anisotropic etching or plasma etching techniques. The silicon layermay be protected against etching by an oxide layer that is by forming aSiO₂ layer. Patterns may be arranged in the SiO₂ layer by means oflithographic technologies. Also, etching may be selectively stopped bydoping the silicon and using p.n. etch stop or other etch stoptechniques. Since all these process steps are well known in the art theyare not described in detail here.

[0061] The above described technology is also suitable for producing amatrix or mould for moulding or casting devices of the invention in e.g.plastic.

[0062] The piezoelectric element providing the mechanical oscillationsis preferably of the so-called multi-layer type, but a bimorphpiezoceramic element may also be used as well as any other kind ofultrasound generating element with suitable dimensions.

[0063] An appreciated application of an embodiment of the invention isin the field of cleaning a patient's blood during surgical operations.The object in this field is to sort out the red blood cells from thecontaminated plasma. Contamination could include air bubbles, fatparticles, coagulation products and other not desirable biologicalmaterial. The red cells will thereafter be brought back to the patient'scirculation. One disadvantage with prior art in the form of centrifugesis that the red blood cells can become deformed, a disadvantage that isnot present with a device according to the present invention.

[0064] Depending on the application, the shape and dimensions of thechannel, the length of the stem 110 and the arms 120, 130, 140, and thefrequency of the ultrasound may vary. In an application for separatingout red blood cells from diluted blood recovered from a patient during asurgical operation, the channel is preferably rectangular incross-section and the stem part of the channel has a width of 700 μm fora one-node standing wave ultrasound field. Greater widths will beappropriate for standing wave ultrasound fields with more nodes.

[0065] The mechanical tolerance of the width of the channel isimportant. The difference should preferably be less than a few percentof half the wavelength of the frequency used in the material/the fluidconcerned.

[0066]FIG. 15 shows a separation unit comprising eight channel units1501-1508, which units are supplied with fluid from a distributioncavity 1510 having one inlet 1512 and eight outlets 1521-1528. Eachchannel unit 1501-1508 is provided with three outlets, one centraloutlet 1541 and two lateral outlets. Said lateral outlets are connectedin pairs, except for the two most lateral outlets of the separation unit1500, forming nine intermediate outlets 1531-1539. Said intermediateoutlet are connected to a fast collecting cavity (not shown)alternatively to a first collecting manifold (not shown). The centraloutlets 1541-1548 are connected to a second collecting cavityalternatively to a second collecting manifold (neither shown).

[0067]FIG. 16 shows the separation unit 1500 of FIG. 15 in a perspectiveview. The plate 1602 in which the separation unit 1500 is formed isarranged on top of an ultrasound source 1620, preferably a piezoelectricelement 1620 and a support structure 1612. An inlet tube 1610 isconnected to the distribution cavity inlet 1542 to provide an inlet forthe fluid connectable to outside tubing.

[0068] A first outlet tube 1631 is providing a connection from the nineintermediate outlets 1531-1539 via a first collecting manifold to a freeend 1641 of said first outlet tube 1631. A second outlet tube 1632 isproviding a connection from the eight central outlets 1541-1548 via asecond collecting manifold to a free end 1642 of said second outlet tube1632.

[0069]FIG. 17 shows a serial arrangement in a plate 1701 of two channelunits, devised to increase particle separation from a fluid. A firstchannel unit 1710 is formed in the plate 1702 having a central branch1712, which branch is connected to a base channel 1721 of a secondchannel unit 1720. Each channel unit is provided with ultrasound energyfrom piezoelectric elements arranged under the plate 1701 at positionsapproximately under a portion of the base channel of each channel unitas indicated by rectangles 1716, 1726.

[0070]FIG. 18 show a channel unit 1800 used to separate a fluidcontaining two types of particles, indicated as black and white,respectively.

[0071] When fluid flows in the direction of the arrow 1804,ultrasound-standing waves are separating the particles in the channelunit into three fluid layers 1801-1803. The position of the ultrasoundsource is indicated by the rectangle 1810.

[0072] The described process separating two types of particles isillustrating a solution to the need within the field of medicaltechnology to separate blood components from each other, i.e. red andwhite blood cells and platelets (erythrocytes, leukocytes andthrombocytes), also called the formed elements of the blood.

[0073] Known art in the field comprises mainly or solely solutions basedon centrifugation. A disadvantage is that it is very difficult to obtaina complete separation of the formed elements, instead a so-called “buffycoat” is obtained. This buffy coat comprises a high concentration ofthrombocytes, leukocytes and a low concentration of erythrocytes. Inthis context one should bear in mind that the sensitive thrombocyteshave been centrifugated and subjected to high g-forces, which probablyhave induced an impaired function within said erythrocytes.

[0074] An embodiment of the present invention can be used to separatethrombocytes and leukocytes from erythrocytes, because they possessdifferent densities as can be seen in table 1. Blood consists of plasmaand formed elements. TABLE 1 Relative density Standard deviationParticles Erythrocytes 1.09645 0.0018 Leukocytes 1.07-1.08 N/AThrombocytes 1.0645 0.0015 Fluids Plasma 1.0269 0.0009 Glucose 30% 1.100 Glucose 50% 1.17 0 Addex electrolyte 1.18 0

[0075] Other solutions possible, iodine control agents.

[0076] As can be seen in table 1, different components have differentdensity. The variation in density is very small for the table entries.When ordinary blood is separated, a channel unit will separate allformed elements in the same way, because their density is higher thanthe medium they are suspended in, i.e. the plasma.

[0077] As an alternative embodiment, the medium is modified, i.e. theplasma is modified so that its density is altered, giving thepossibility to separate the different blood cells. This is achieved byadding an amount of denser liquid to the plasma and thereby dilute theplasma to a lower concentration, but with a higher density.

EXAMPLES

[0078] Take 100 ml blood with a haematocrit of 40%. This entails that60% (=60 ml) of the blood is plasma. The plasma has a density of 1.0269.By adding 30 ml of 50% glucose solution we get according to the formula:$d_{tot} = \frac{{v_{1}*d_{1}} + {v_{2}*d_{2}}}{v_{1} + v_{2}}$

[0079] where

[0080] v₁ is the volume of the first fluid

[0081] d₁ is the density of the first fluid

[0082] v₂ is the volume of the second fluid

[0083] d₂ is the density of the second fluid

[0084] d_(tot) is the density of the mix

[0085] The density of the mix medium becomes 1.0746.

[0086] When this mixture is entered in an embodiment, a separation isachieved where thrombocytes and erythrocytes are directed into separatebranches, because now the thrombocytes are lighter than the medium.

[0087] This is of course just an example. It is also possible toseparate out leukocytes because they have a specific weight, differentfrom the one of erythrocytes and thrombocytes. It should also bepossible to separate out bacteria and virus with this method. The methodcan be used on all solutions except those solutions where it isimpossible or otherwise inappropriate to manipulate the density of thesolution. It is also possible to separate out bacteria and stem cellsfrom cultures of the same, having them suspended in a suitable solution.

[0088]FIG. 19 and FIG. 20 shows a channel unit with three inlets A,B,Aand three outlets C,D,C. A first fluid is fed to the channel unit atboth A-inlets and a second fluid is fed to the B inlet. At thismicroscale, the fluids will not blend.

[0089]FIG. 20 shows how particles from the fluid entered at the A-inletsare forced by the ultrasound standing wave field to migrate over to thefluid entered at the B-inlet. This type of “separation” is especiallyuseful when the objective is to keep formed elements of the blood anddiscard the plasma, as in e.g. plasmapheresis, and in blood washapplications where blood cells in contaminated plasma (A) are moved to aclean solution (B) and finally blood cells in a clean medium is produced(D). The waste plasma (C) is discarded. This method will enable a highlyefficient blood wash with very low amounts of washing substance needed.

[0090]FIGS. 21 and 22 show a radial arrangement of the channel units,said arrangement being particularly advantageous when base material ofthe plate are circular discs or the like.

[0091] It will be appreciated by persons skilled in the art that thestructure of the device according to the present invention has severaladvantages including ease of manufacture and solving of the problem ofseparating particles liable to disintegration in filtering andcentrifugation processes.

1. A device for separating suspended particles from a fluid, comprisinga channel unit arranged in a plate having first and second opposinggreat surfaces, said channel unit including a base stem channel havingsubstantially parallel or near parallel base stem walls perpendicular tosaid surfaces, said base stem channel having an inlet and, opposite saidinlet, a branching point connected to two or more different outlets; andoscillation means for delivering mechanical energy to a fluid in saidchannel unit, such that said particles are concentrated into laminarlayers in the base stem channel, substantially parallel to said basestem walls, wherein said branching point is devised to separateparticles, arranged in said laminar layers in a fluid flowing in saidbase stem channel, to said different outlets, wherein said channel unitis formed as a part of a material layer close to said first greatsurface, and said oscillation means are arranged in contact with saidsecond great surface for delivering mechanical energy to said plate suchthat a standing wave field is created between said base stem walls.
 2. Adevice according to claim 1, wherein said oscillation means are arrangedto deliver mechanical energy in a direction perpendicular to the firstand second surfaces of said plate.
 3. A device according to claim 1further comprising a control unit capable of controlling saidoscillation means to deliver mechanical energy of controlled frequencyand power within the ultrasound frequency band and with the frequencybeing so adapted to the dimensions of the channel unit that in a widthof the channel, between base stem walls, an acoustic standing wave fieldis created.
 4. A device according to claim 1, wherein a number ofchannel units are arranged in the same plate receiving mechanical energyfrom a single oscillation means allowing for integration of a largenumber of channel units for separation purposes on a single plate.
 5. Adevice according to claim 1, wherein the channel unit is provided withan inlet and three outlets.
 6. A device according to claim 1, whereinthe plate comprises a piece of homogenous material in which said channelunit is defined.
 7. A device according to claim 6, wherein the firstsurface of said plate is covered by a layer of glass.
 8. A deviceaccording to claim 7, wherein said plate and said layer of glass arebonded together.
 9. A device according to claim 1, wherein said plate ismade of silicon.
 10. A device according to claim 1, wherein said plateis made of plastic.
 11. A device according to claim 1, wherein thebranching point is shaped like a cross, and the inlet is located at thelower end of the cross base stem and the three outlets are located atthe top of the cross.
 12. A device according to claim 1, wherein thebranching point divides the base stem into three arms with angles α1 andα2 between them, and that the value of α1 and α2 are between 0 and 90degrees.
 13. A device according to claim 1, wherein the branching pointcomprises the division of the base stem directly into three parallelchannels divided by thin dividing walls.
 14. A device according to claim13 wherein the thin walls have a thickness of between 1 and 40micrometer, preferably 20 micrometer.
 15. A device according to claim 1,wherein the width of the channel is in the range between 60 and 1400micrometer.
 16. A device according to claim 1, wherein the width of thechannel is 700 micrometer.
 17. A device according to claim 1, whereinsaid oscillation means comprises a piezoelectric element.
 18. A deviceaccording to claim 17, wherein said mechanical energy is of controlledfrequency and power inside the ultrasound frequency band.
 19. A deviceaccording to claim 18, wherein the electrical energy is controllablewith regard to waveform, frequency and power.
 20. A device according toclaim 19, wherein the waveform is controllable to be one of but notlimited to sinus wave, triangular wave or square wave.
 21. A deviceaccording to claim 1, wherein the dimensions of the channel unit, i.e.the width and a height of the channel, the frequency of the oscillationmeans and a flow rate is adapted to accommodate blood as said fluid andthe red blood cells as the particles to be separated from the fluid. 22.A device according to claim 1, wherein the dimensions of the channelunit, i.e. the width and a height of the channel, the frequency of theoscillation means and a flow rate is adapted to handle a fluidcontaining particles of biological material containing fat.
 23. A deviceaccording to claim 1, wherein the channel unit is provided with threeinlets and three outlets.
 24. A device according to claim 22, whereinthe dimensions of the channel unit, i.e. the width and a height of thechannel, the frequency of the oscillation means are adapted to handle afluid containing platelets.
 25. A separator unit for use in a deviceaccording to claim 1, wherein said separator unit comprises a platehaving first and second opposing great surfaces, and in that a channelunit is formed as a part of a material layer close to said first greatsurface, said channel unit including a base stem channel havingsubstantially parallel or near parallel base stem walls perpendicular tosaid surfaces, said base stem channel having an inlet and, opposite saidinlet, a branching point connected to two or more different outlets, andwherein said second surface is connectable to oscillation means fordelivering mechanical energy to a fluid in said channel unit.
 26. Aseparator unit according to claim 25, wherein a number of channel unitsare arranged in the same plate, for receiving mechanical energy from asingle oscillation means.
 27. A separator unit according to claim 25,wherein the plate comprises a piece of homogenous material in which saidchannel unit is defined.
 28. A separator unit according to claim 27,wherein said homogenous material is plastic.
 29. A separator unitaccording to claim 27, wherein said homogeneous material is silicon. 30.A separator unit according to claim 27, wherein the first surface ofsaid plate is covered by a sealing layer which makes it possible tovisually inspect a separation process in said channel.
 31. A separatorunit according to claim 30, wherein the sealing layer is made of glass.32. A separator unit according to claim 31, wherein said plate and saidlayer of glass are bonded together.
 33. A method for separatingparticles from fluids using ultrasound, laminar flow, and stationarywave effects comprising the steps of: feeding a fluid to a separatorunit comprising a plate having first and second opposing great surfacesand a channel unit formed as a part of a material layer close to saidfirst surface, forcing the fluid to a substantially laminar flow in aflow direction; applying an ultrasound oscillating wave field to saidsecond surface, thereby subjecting said flow to an ultrasound stationarywave field during its flow past a distance in said channel unit, forcingsaid particles to a non-uniform distribution in a separation directionparallel to said surfaces and perpendicular to the flow direction; andseparating said second laminar flow into a first and a second separatedflow in such a way that the concentration of particles is higher in thefirst separated flow than in the second separated flow.
 34. The methodaccording to claim 33, wherein said ultrasound oscillating wave field isgiven a frequency adapted to a width of the channel unit, such thatvibrations in the plate give rise to said wave field parallel with theplate.
 35. The method according to claim 33, wherein said ultrasoundoscillating wave field is applied perpendicular to said surfaces of theplate.
 36. The method according to claim 33, further comprising the stepof separating out particles of biological material containing fat from afluid.
 37. The method according to claim 33, further comprising the stepof separating particles from blood.
 38. The method as recited in claim33, further comprising the step of separating out bacteria from a fluid.39. The method as recited in claim 33, further comprising the step ofseparating out stem cells from a fluid.
 40. The method as recited inclaim 33, further comprising the step of separating out platelets from afluid.
 41. The method as recited in claim 33, further comprising thestep of adding a solution to the original fluid, said solution having adifferent density than the original fluid, with the purpose of alteringthe density of the fluid from which particles are to be separated. 42.The method according to claim 33, wherein the method is repeated in anumber of stages.
 43. The method according to claim 42, wherein newfluid is introduced before the steps are repeated.
 44. The methodaccording to claim 33, further comprising the step of controlling thepower fed to the ultrasound stationary wave field by means ofcontrolling the electrical energy with regard to waveform, frequency andpower to a piezoelectric element transmitting its mechanical energy tothe fluid and its surroundings.